Several publications and patent documents are cited throughout the specification in order to describe the state of the art to which this invention pertains. Each of these citations is incorporated by reference herein as though set forth in full.
The poxviridae comprise a large family of complex DNA viruses that replicate in the cytoplasm of vertebrate and invertebrate cells. In humans, smallpox was by far the most important poxvirus infection. The causative agent of smallpox is the variola virus, a member of the genus Orthopoxvirus. Vaccinia virus, also a member of the genus Orthopoxvirus in the family of Poxviridae, was used as live vaccine to immunize against smallpox. Successful worldwide vaccination with Vaccinia virus culminated in the eradication of variola virus (The global eradication of smallpox. Final report of the global commission for the certification of smallpox eradication; History of Public Health, No. 4, Geneva: World Health Organization, 1980). However, smallpox or smallpoxlike diseases still pose a major potential health problem. Additionally, certain pox virus infections cause great damage to livestock and wild life populations and are often require costly eradication procedures.
By inducing an anti-viral state in cells (1) and modulating the immune response (2), IFNs are major mediators of the anti-viral defense (3). Thus, the interferon (IFN) pathway is one of the most frequent targets of immune response modifiers (IRMs) encoded by viruses (1, 4) including OPVs (5). Type I IFN-α and -β signal through a common receptor (IFN-α/βR) which is expressed at the surface of the majority of cells (6). Most OPVs encode a high affinity type I IFN binding protein (bp) supposed to inhibit type I IFN signaling by sequestering Type I IFNs away from the IFN-α/βR (7-11). In the case of ECTV, the Type I IFN by is encoded in gene EVM166 and binds with high affinity to mouse IFN-α but, surprisingly, not-β (7) (herein eIFN-α bp). While it is presumed that IRMs are important for OPV virulence, only a few studies have been performed in vivo with OPVs in their natural hosts. Studying the role of IRMs in natural hosts is essential to understand virus virulence, define new targets of anti-viral therapies, and test the possibility of using secreted IRMs as targets of subunit anti-viral vaccines.